Clinicopathologic and Molecular Characteristics of Epstein-Barr Virus-Associated Smooth Muscle Tumor Compared With Those of Leiomyoma and Leiomyosarcoma.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (EBV-SMTs) are rare smooth muscle neoplasms exclusively associated with immunosuppression, such as in patients with HIV/AIDS, posttransplant, and congenital immunodeficiency. However, the genomic landscape of EBV-SMTs is poorly understood. Leiomyosarcomas harbor genomic instability and multiple recurrent DNA copy number alterations, whereas leiomyomas lack such changes. Thus, this study aimed to fill this knowledge gap by characterizing copy number alterations in EBV-SMTs and correlating this information with clinicopathologic characteristics. Our study investigated and compared the pathologic characteristics and copy number profiles of 9 EBV-SMTs (from 7 post-transplant and AIDS patients), 6 leiomyomas, and 7 leiomyosarcomas, using chromosomal microarray platforms. Our results showed a lower copy number alteration burden in EBV-SMTs and leiomyoma than in leiomyosarcoma. This contrast in the molecular profile between EBV-SMTs and leiomyosarcoma is concordant with the different clinical behaviors and pathologic characteristics exhibited by these tumors. Despite having an overall copy number alteration profile closer to leiomyoma, recurrent copy number gain of oncogenes, such as RUNX1, CCND2, and ETS2, was found in EBV-SMTs. Epigenetic alterations may play an important role in tumorigenesis as recurrent copy number gains were found in histone deacetylases. A gene enrichment analysis also demonstrated enrichment of genes involved in the host response to viral infection, suggesting that the tumor immune microenvironment may play an important role in EBV-SMT tumorigenesis.

Homologous recombination repair gene mutations in Malaysian prostate cancer patients.

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.

A Clinicopathology Review and Update of Epstein-Barr Virus-Associated Mesenchymal Tumors.

The Epstein-Barr virus (EBV) is associated with various tumor types, including nasopharyngeal carcinoma and lymphoproliferative disorders. While much is known about EBV-related epithelial and lymphoid tumors, there is a paucity of knowledge concerning EBV-associated mesenchymal tumors. This review aims to provide a comprehensive overview of EBV-associated mesenchymal tumors, encompassing their clinical features, pathological characteristics, pathophysiology, prognostic factors, and current treatment approaches. Through an extensive literature search using the PubMed database, we were able to identify three distinct EBV-associated mesenchymal tumors: EBV-associated smooth muscle tumors, inflammatory pseudotumor-like follicular dendritic cell sarcomas, and EBV-associated osteosarcomas. Although this review extensively explored the different aspects of these mesenchymal tumors, our comprehension of the underlying pathophysiology in this context is still incomplete. Therefore, we hope that this review paper will not only serve as a valuable repository of information but also serve as a catalyst for prospective in vitro and in vivo research studies to bridge the existing knowledge gap surrounding pathophysiology, ultimately making an important contribution to shaping future therapeutic approaches.

αvß1 integrin is enriched in extracellular vesicles of metastatic breast cancer cells: A mechanism mediated by galectin-3.

Breast cancer cells release a large quantity of biocargo-bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV-bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and ß1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular-body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early-stage patients. With a magnetic bead-based flow cytometry assay, we confirmed that integrins αv and ß1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvß1 into EVs. In particular, knockdown of galectin-3, but not galectin-1, causes a reduction in the levels of cell surface integrins ß1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin-3 leads to a decrease of integrin αvß1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvß1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvß1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV-bound integrin αvß1 with breast cancer metastasis and provide additional insights into the export of integrin αvß1 into EVs in the context of metastasis.